Synergism between arsenite and proteasome inhibitor MG132 over cell death in myeloid leukaemic cells U937 and the induction of low levels of intracellular superoxide anion

Caffeic acid phenylethyl ester and MG132, two novel nonconventional chemotherapeutic agents, induce apoptosis of human leukemic cells by disrupting mitochondrial function

“…In a more recent study, we assessed the potential of MG132 and CAPE to sensitize leukemic cells to arseniteinduced cytotoxicity and we found that MG132+arsenite were synergic in promonocytic leukemia cells, while CAPE+arsenite were antagonistic [43]. Since both CAPE and arsenite target the mitochondria and increase ROS as one of their main mechanisms, these results highlight that both in-depth mechanistic approaches and a thorough analysis of drug interaction are needed to demonstrate potential efficacy in preclinical studies [44].…”

MG132-mediated inhibition of the ubiquitin–proteasome pathway ameliorates cancer cachexia

“…Recently, the therapeutic potential of MG132 for cancer treatment has been evaluated. Regardless of cancer type, MG132 is a promising anti-cancer agent functioning by inhibiting tumor cell growth and inducing cancer cell apoptosis (Guo 2012;Sung et al 2012;Zanotto-Filho et al 2012;Lombardo et al 2012). In the present study, we showed that skeletal muscle atrophy induced by cachexia was significantly reversed with MG132 treatment.…”

Synergism of arsenic trioxide and MG132 in Raji cells attained by targeting BNIP3, autophagy, and mitochondria with low doses of valproic acid and vincristine

“…The Chou-Talalay combination index (CI) method provides a valuable assessment of cytotoxic drug interaction since it can describe whether a combination of drugs is synergic (CI < 1), additive (CI = 1) or antagonistic (CI > 1) over an entire range of cytotoxic effects [7,8]. By using the CI method we have previously demonstrated that ATO combined with the proteasome inhibitor MG132 are synergic in the promonocytic leukaemia cell line U937 and antagonistic in Burkitt's lymphoma cell line Raji [9]. It is useful to bring together results of cytotoxic drug interaction studies with known mechanistic models because the latter provide a rationale to target cell death resistance and the former may conclude on the pharmacological relevance of the targeted mechanism, particularly if antagonism is turned into synergism.…”